Abstract
MicroRNAs (miRNAs) act as a kind of small and noncoding RNA, which have been implicated in the regulation of various pathobiological processes in cancer, including progression in pancreatic cancer and in other human cancers. Previous reports demonstrate that pancreatic cancer has been reported as one of the leading causes of cancer-related death, and some factors including oncogenic genes and environments are involved in tumorigenesis. In our study, we found microRNA-146a (miR-146a) was evidently downregulated in pancreatic cancer tissues and cells. Overexpression of miR-146a obviously reduced cell proliferation and tumorigenesis in vitro, as determined by MTT analysis, colony formation analysis, EdU analysis, and cell cycle experiments. Here, we found tumor suppressor sex-determining region Y-box 7 (SOX7) was the direct target of miR-146a. Overexpression of miR-146a decidedly inhibited SOX7 expression, which promotes cell proliferation and tumorigenesis. Knockdown of miR-146a increased SOX7 expression. Depression of miR-146a and SOX7 promoted cell proliferation and tumorigenesis in vitro, confirming miR-146a regulated pancreatic cancer cell proliferation by inhibiting SOX7. In summary, we found miR-146a reduced the cell proliferation of pancreatic cancer through targeting SOX7. In the present study, we demonstrated the function of miR-146a in pancreatic cancer and might provide a new target in the treatment of pancreatic cancer.
Highlights
Pancreatic cancer (PC) is defined as a malignancy at digestive tract, featured by insidious initiation and rapid progression [1, 2]
We investigated the role of miR-146a in PC and addressed the mechanism how miR-146a regulates sex-determining region Y-box 7 (SOX7) in PC. e study might provide a new molecular target for the diagnosis and treatment of PC
We observed the downregulation of miR-146a in the human pancreatic cancer cell lines tested (BxPC3, SW1990, Panc-1, PCI-35, and JF-305) compared with the normal human pancreatic duct epithelial cell HPCY5, as well as in pancreatic tumor tissues by clinical results
Summary
Pancreatic cancer (PC) is defined as a malignancy at digestive tract, featured by insidious initiation and rapid progression [1, 2]. Previous research studies have proved miR-146a as a specific suppressor miRNA in many kinds of tumors that acts by repressing the expression of the proliferation-associated cancer gene or inhibiting tumor metastasis [7, 8]. A previous study demonstrated that the expression of SOX7 mRNA was frequently downregulated in many human cancer cell lines and tumor tissues [12]. Ectopic SOX7 expression inhibits proliferation, migration, and invasion of breast cancer cells in vitro and tumor growth in vivo [16]. Its role is finely interpreted in multiple human cancers and can be regulated by miRNAs in cancer cells, whether SOX7 can be regulated by miR-146a has not been addressed in pancreatic cancer yet. We investigated the role of miR-146a in PC and addressed the mechanism how miR-146a regulates SOX7 in PC. e study might provide a new molecular target for the diagnosis and treatment of PC
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